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Introduction Stenotrophomonas maltophilia is a bacteria whose role in patients with cystic fibrosis (CF) bronchiectasis has been previously studied; little is known about its role in non-CF bronchiectasis. Materials and methods Aim of our study is to investigate the risk factors for S. maltophilia acquisition and its clinical impact on bronchiectasis patients. A retrospective observational cohort study enrolling patients attending the Bronchiectasis Clinic at the Royal Infirmary of Edinburgh, Scotland, UK. A total of 167 bronchiectasis patients undergoing intravenous (IV) antibiotic therapy were selected and divided according to single or chronic S. maltophilia isolation in sputum. The risk factors and prognostic impact were studied. Results Single isolation was independently associated with lower baseline % predicted forced expiratory volume in 1 s [odds ratio (OR) 0.98; 95% confidence interval (CI) 0.970–1.044; P  = 0.025] and with less radiological involvement (OR 0.379; 95% CI 0.175–0.819; P  = 0.01). Chronic isolation was associated with the number of IV antibiotic courses in the year before and after the first isolation (OR 1.2; 95% CI 1.053–1.398; P  = 0.007) and with the absence of Pseudomonas aeruginosa colonization (OR 0.207; 95% CI 0.056–0.764; P  = 0.02). In the chronic isolation group, there were more exacerbations and more need of IV antibiotics in the year after the first isolation. Conclusions Poor lung function is the main independent risk factor for single isolation of S. maltophilia. For chronic colonization, the main independent risk factor is the number of IV antibiotic courses and the absence of P. aeruginosa chronic colonization. Only when chronically present, S. maltophilia had a clinical impact with more exacerbations. [ABSTRACT FROM AUTHOR]